Association Between False Memories and Delusions in Alzheimer Disease
Authors: Emma McLachlan, Dilek Ocal, Neil Burgess, Suzanne Reeves, Robert Howard, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Zaven Khachaturian, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Jonathan Jackson, Eliezer Masliah, Donna Masterman, Ozioma Okonkwo, Richard Perrin, Laurie Ryan, Nina Silverberg, Adam Fleisher, Diana Truran Sacrey, Juliet Fockler, Cat Conti, Dallas Veitch, John Neuhaus, Chengshi Jin, Rachel Nosheny, Miriam Ashford, Derek Flenniken, Adrienne Kormos, Tom Montine, Michael Rafii, Rema Raman, Gustavo Jimenez, Michael Donohue, Devon Gessert, Jennifer Salazar, Caileigh Zimmerman, Yuliana Cabrera, Sarah Walter, Garrett Miller, Godfrey Coker, Taylor Clanton, Lindsey Hergesheimer, Stephanie Smith, Olusegun Adegoke, Payam Mahboubi, Shelley Moore, Jeremy Pizzola, Elizabeth Shaffer, Brittany Sloan, Danielle Harvey, Arvin Forghanian-Arani, Bret Borowski, Chad Ward, Christopher Schwarz, David Jones, Jeff Gunter, Kejal Kantarci, Matthew Senjem, Prashanthi Vemuri, Robert Reid, Nick C. Fox, Ian Malone, Paul Thompson, Sophia I. Thomopoulos, Talia M. Nir, Neda Jahanshad, Charles DeCarli, Alexander Knaack, Evan Fletcher, Duygu Tosun-Turgut, Stephanie Rossi Chen, Mark Choe, Karen Crawford, Paul A. Yushkevich, Sandhitsu Das, Robert A. Koeppe, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Householder, Erin Franklin, Haley Bernhardt, Lisa Taylor-Reinwald, Magdalena Korecka, Michal Figurski, Scott Neu Neu, Kwangsik Nho, Shannon L. Risacher, Liana G. Apostolova, Li Shen, Tatiana M. Foroud, Kelly Nudelman, Kelley Faber, Kristi Wilmes, Leon Thal, Lisa C. Silbert, Betty Lind, Rachel Crissey, Jeffrey A. Kaye, Raina Carter, Sara Dolen, Joseph Quinn, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Karen Dagerman, Bryan M. Spann, James Brewer, Helen Vanderswag, Jaimie Ziolkowski, Judith L. Heidebrink, Lisa Zbizek-Nulph, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Javier Villanueva-Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass Kass, Rachelle S. Doody, Victoria Shibley Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Akiva Mintz, Beau Ances, David Winkfield, Maria Carroll, Georgia Stobbs-Cucchi, Angela Oliver, Mary L. Creech, Mark A. Mintun, Stacy Schneider, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Daniel Marson, Hillel Grossman, Martin A. Goldstein, Jonathan Greenber, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuels, Ranjan Duara, Maria T. Greig-Custo, Rosemarie Rodriguez, Marilyn Albert, Chiadi Onyike, Leonie Farrington, Scott Rudow, Rottislav Brichko, Stephanie Kielb, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Martin Sadowski, Thomas Wisniewski, Melanie Shulman, Arline Faustin, Julia Rao, Karen M. Castro, Anaztasia Ulysse, Shannon Chen, Mohammed O. Sheikh, Jamika Singleton-Garvin, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Terence Z. Wong, Salvador Borges-Neto, Jason H. Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Charles D. Smith, Gregory A. Jicha, Riham El Khouli, Flavius D. Raslau, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Kim Martin, Nancy Kowalski, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Seleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yanez, Elizabeth Sosa, Megan Witbracht, Brendan Kelley, Trung Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Ihab Hajjar, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Daniel H.S. Silverman, Sarah Kremen, Liana Apostolova, Kathleen Tingus, Po H. Lu, George Bartzokis, Ellen Woo, Edmond Teng, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Adam P. Mecca, Susan P. Good, Martha G. MacAvoy, Richard E. Carson, Pradeep Varma, Howard Chertkow, Susan Vaitekunis, Chris Hosein, Sandra Black, Bojana Stefanovic, Chris (Chinthaka) Heyn, Ging-Yuek Robin Hsiung, Ellen Kim, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternak, Irina Rachinsky, Andrew Kertesz, Dick Drost, John Rogers, Ian Grant, Brittanie Muse, Emily Rogalski, Jordan Robson, M. Marsel Mesulam, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Kristine Liposki, Sandra Weintraub, Borna Bonakdarpour, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Howard J. Rosen, Bruce L. Miller, David Perry, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Kelly McCann, Jessica Poe, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome Yesavage, Joy L. Taylor, Steven Chao, Jaila Coleman, Jessica D. White, Barton Lane, Allyson Rosen, Jared Tinklenberg, Christine M. Belden, Alireza Atri, Kelly A. Clark, Edward Zamrini, Marwan Sabbagh, Ronald Killiany, Robert Stern, Jesse Mez, Neil Kowall, Andrew E. Budson, Thomas O. Obisesan, Oyonumo E. Ntekim, Saba Wolday, Javed I. Khan, Evaristus Nwulia, Sheeba Nadarajah, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Pauline Maillard, John Olichney, Owen Carmichael, Vernice Bates, Horacio Capote, Michelle Rainka, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Allison Perrin, Anna Burke, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, David Hart, Earl A. Zimmerman, Dzintra Celmins, Delwyn D. Miller, Laura L. Boles, Karen Ekstam Smith, Hristina Koleva, Hyungsub Shim, Ki Won Nam, Susan K. Schultz, Jeff D. Williamson, Suzanne Craft, Jo Cleveland, Mia Yang, Kaycee M. Sink, Brian R. Ott, Jonathan Drake, Geoffrey Tremont, Lori A. Daielllo, Aaron Ritter, Charles Bernick, Donna Munic, Abigail O'Connelll, Jacobo Mintzer, Arthur Wiliams, Joseph Masdeu, Jiong Shi, Angelica Garcia, Paul Newhouse, Steven Potkin, Stephen Salloway, Paul Malloy, Stephen Correia, Smita Kittur, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Athena Lee, Thomas Neylan, Jordan Grafman, Sarah Danowski, Catherine Nguyen-Barrera, Jacqueline Hayes, Shannon Finley, Matthew Bernstein, Norm Foster, Sungeun Kim, Ajay Sood, Kimberly S. Blanchard, Konstantinos Arfanakis, Debra Fleischman, Daniel Varon, Christopher Reist, Carl Sadowsky, Walter Martinez, Teresa Villena, Elaine R. Peskind, Eric C. Petrie, Gail Li, Scott Mackin, Erin Drake, Craig Nelson, David Bikford, Meryl Butters, Michelle Zmuda, Denise Reyes, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, Dariella Fernandez
Journal: JAMA Psychiatry (2023)

Importance Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories. Objective To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions. Design, Setting, and Participants Since the Alzheimer’s Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021. Exposure Enrollment in the ADNI. Main Outcomes and Measures The main outcomes included false recognition, measured with the 13-item Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions. Results Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P &amp;amp;lt; .001), right hippocampal volume (0.94 [0.92-0.97], P &amp;amp;lt; .001), left entorhinal cortex volume (0.94 [0.91-0.97], P &amp;amp;lt; .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P &amp;amp;lt; .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P &amp;amp;lt; .001). There was no overlap between locations associated with false recognition and those associated with delusions. Conclusions and Relevance In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis.